School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
Drug Des Devel Ther. 2023 Feb 23;17:597-612. doi: 10.2147/DDDT.S398808. eCollection 2023.
Atherosclerosis (AS) is an immunoinflammatory disease associated with dyslipidemia. Zhuyu Pill (ZYP) is a classic Chinese herbal compound that has been shown to exhibit anti-inflammatory and lipid-lowering effects on AS in our previous studies. However, the underlying mechanisms by which ZYP ameliorates atherosclerosis have not yet been fully investigated. In this study, network pharmacology and in vivo experiments were conducted to explore the underlying pharmacological mechanisms of ZYP on ameliorating AS.
The active ingredients of ZYP were acquired from our previous study. The putative targets of ZYP relevant to AS were obtained from TCMSP, SwissTargetPrediction, STITCH, DisGeNET, and GeneCards databases. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted using the Cytoscape software. Furthermore, in vivo experiments were carried out for target validation in apolipoprotein E (ApoE) -/- mice.
Animal experiments revealed that ZYP ameliorated AS mainly through lowering blood lipids, alleviating vascular inflammation, and decreasing the levels of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM1), monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, the results of Real-Time quantitative PCR revealed that ZYP inhibited the gene expressions of mitogen-activated protein kinase (MAPK) p38, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) p65. The Immunohistochemistry and Western blot assays showed the inhibitory effect of ZYP on the proteins level of p38, p-p38, p65, and p-p65.
This study has provided valuable evidence on the pharmacological mechanisms of action of ZYP in ameliorating AS that will be useful for forming the rationale of future research studying the cardio-protection and anti-inflammation effects of ZYP.
动脉粥样硬化（AS）是一种与血脂异常相关的免疫炎症性疾病。竹节参丸（ZYP）是一种经典的中药复方，在我们之前的研究中已显示出对 AS 的抗炎和降脂作用。然而，ZYP 改善动脉粥样硬化的潜在机制尚未得到充分研究。在这项研究中，我们通过网络药理学和体内实验来探讨 ZYP 改善动脉粥样硬化的潜在药理机制。
从我们之前的研究中获得 ZYP 的活性成分。从 TCMSP、SwissTargetPrediction、STITCH、DisGeNET 和 GeneCards 数据库中获得与 AS 相关的 ZYP 的潜在靶点。使用 Cytoscape 软件进行蛋白质-蛋白质相互作用（PPI）网络、基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。此外，在载脂蛋白 E（ApoE）-/-小鼠中进行体内实验以验证靶点。
动物实验表明，ZYP 通过降低血脂、减轻血管炎症和降低血管细胞间黏附分子-1（VCAM1）、细胞间黏附分子-1（ICAM1）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）水平来改善 AS。此外，实时定量 PCR 的结果表明，ZYP 抑制丝裂原活化蛋白激酶（MAPK）p38、细胞外调节蛋白激酶（ERK）、c-Jun N-末端激酶（JNK）和核因子 kappa-B（NF-κB）p65 的基因表达。免疫组织化学和 Western blot 检测显示 ZYP 对 p38、p-p38、p65 和 p-p65 蛋白水平的抑制作用。
本研究为 ZYP 改善 AS 的药理作用机制提供了有价值的证据，这将有助于形成未来研究 ZYP 的心脏保护和抗炎作用的基础。
